TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27711	83356;83357;83358	chr2:178563001;178563000;178562999	chr2:179427728;179427727;179427726
N2AB	26070	78433;78434;78435	chr2:178563001;178563000;178562999	chr2:179427728;179427727;179427726
N2A	25143	75652;75653;75654	chr2:178563001;178563000;178562999	chr2:179427728;179427727;179427726
N2B	18646	56161;56162;56163	chr2:178563001;178563000;178562999	chr2:179427728;179427727;179427726
Novex-1	18771	56536;56537;56538	chr2:178563001;178563000;178562999	chr2:179427728;179427727;179427726
Novex-2	18838	56737;56738;56739	chr2:178563001;178563000;178562999	chr2:179427728;179427727;179427726
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-141
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.3122
• Predicted PPI site: I

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
K/E	rs377621382	None	0.716	D	0.467	0.413	0.352910780287	gnomAD-4.0.0	1.59148E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43271E-05	0
K/T	rs1249941262	-0.688	0.946	D	0.719	0.39	0.37479162749	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
K/T	rs1249941262	-0.688	0.946	D	0.719	0.39	0.37479162749	gnomAD-4.0.0	1.59176E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85887E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
K/A	0.9606	likely_pathogenic	0.9549	pathogenic	-1.038	Destabilizing	0.87	D	0.558	neutral	None	None	None	None	I
K/C	0.9578	likely_pathogenic	0.9611	pathogenic	-1.095	Destabilizing	0.998	D	0.8	deleterious	None	None	None	None	I
K/D	0.9898	likely_pathogenic	0.9866	pathogenic	-0.667	Destabilizing	0.959	D	0.763	deleterious	None	None	None	None	I
K/E	0.9225	likely_pathogenic	0.9053	pathogenic	-0.485	Destabilizing	0.716	D	0.467	neutral	D	0.534387601	None	None	I
K/F	0.976	likely_pathogenic	0.9746	pathogenic	-0.557	Destabilizing	0.998	D	0.791	deleterious	None	None	None	None	I
K/G	0.9757	likely_pathogenic	0.9687	pathogenic	-1.469	Destabilizing	0.959	D	0.711	prob.delet.	None	None	None	None	I
K/H	0.8175	likely_pathogenic	0.7939	pathogenic	-1.767	Destabilizing	0.994	D	0.753	deleterious	None	None	None	None	I
K/I	0.8898	likely_pathogenic	0.8673	pathogenic	0.124	Stabilizing	0.979	D	0.811	deleterious	None	None	None	None	I
K/L	0.8489	likely_pathogenic	0.8266	pathogenic	0.124	Stabilizing	0.959	D	0.711	prob.delet.	None	None	None	None	I
K/M	0.7342	likely_pathogenic	0.7052	pathogenic	-0.003	Destabilizing	0.998	D	0.747	deleterious	D	0.534134112	None	None	I
K/N	0.9661	likely_pathogenic	0.9525	pathogenic	-1.023	Destabilizing	0.946	D	0.652	neutral	D	0.522613222	None	None	I
K/P	0.9883	likely_pathogenic	0.9869	pathogenic	-0.235	Destabilizing	0.979	D	0.774	deleterious	None	None	None	None	I
K/Q	0.6822	likely_pathogenic	0.6534	pathogenic	-0.982	Destabilizing	0.946	D	0.639	neutral	N	0.510749938	None	None	I
K/R	0.1298	likely_benign	0.1185	benign	-0.914	Destabilizing	0.035	N	0.303	neutral	N	0.487670318	None	None	I
K/S	0.9847	likely_pathogenic	0.9793	pathogenic	-1.73	Destabilizing	0.87	D	0.545	neutral	None	None	None	None	I
K/T	0.9245	likely_pathogenic	0.9089	pathogenic	-1.309	Destabilizing	0.946	D	0.719	prob.delet.	D	0.522359733	None	None	I
K/V	0.8783	likely_pathogenic	0.8633	pathogenic	-0.235	Destabilizing	0.959	D	0.775	deleterious	None	None	None	None	I
K/W	0.975	likely_pathogenic	0.9701	pathogenic	-0.429	Destabilizing	0.998	D	0.792	deleterious	None	None	None	None	I
K/Y	0.9366	likely_pathogenic	0.9217	pathogenic	-0.118	Destabilizing	0.993	D	0.791	deleterious	None	None	None	None	I

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.